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Irinotecan (CPT-11) Canonical Anti-Cancer Drug Can also Modulate Antiviral and Pro-Inflammatory Responses of Primary

Anthony Dobi1, Philippe Gasque1,2, Pascale Guiraud1

  • 1Unité de Recherche en Pharmaco-Immunologie (UR-EPI), Université et CHU de La Réunion (Site Félix Guyon), 97400 Saint-Denis, France.

Cells
|July 2, 2021
PubMed

Insights

Irinotecan, an anti-cancer drug, may treat chronic viral arthritis. It boosts antiviral responses and reduces inflammation in joint cells, suggesting therapeutic potential for alphavirus-induced conditions.

Area of Science:

  • Virology
  • Immunology
  • Rheumatology

Background:

  • Alphaviruses cause chronic inflammatory rheumatisms.
  • No specific vaccines or antiviral therapies exist for alphavirus diseases.
  • Primary human synovial fibroblasts (HSF) are key stromal cells in joint synovium.

Purpose of the Study:

  • To evaluate repositioning the anti-cancer drug irinotecan.
  • To assess irinotecan's modulation of antiviral and inflammatory responses in HSF.
  • To investigate irinotecan's potential in treating alphavirus-induced arthritis.

Main Methods:

  • HSF cells were exposed to O'nyong-nyong virus (ONNV) and polyinosinic-polycytidylic acid (PIC) to simulate infections.
  • Interleukin-1β (IL-1β) stimulated pro-inflammatory responses.
  • Quantitative RT-PCR analyzed gene expression, including interferon-stimulated genes and inflammatory markers (CXCL8, IL-6, COX-2).
  • Regulation of STAT1, STAT2, p53, and NF-κB gene expression was assessed.

Main Results:

  • Irinotecan (15 µM) amplified antiviral gene expression in PIC-stimulated HSF.
  • Irinotecan reduced pro-inflammatory gene expression (CXCL8, IL-6, COX-2) in IL-1β-treated HSF.
  • These effects were linked to the regulation of STAT1, STAT2, p53, and NF-κB.
  • Irinotecan did not affect responses in untreated or ONNV-stimulated cells.

Conclusions:

  • Irinotecan shows potential for treating chronic, severe viral arthritis.
  • The drug modulates antiviral and inflammatory pathways in joint cells.
  • Irinotecan may be a therapeutic option for non-acute viral-induced rheumatic conditions.
Keywords:
alphavirus infectionantiviral responsearthritishuman synovial fibroblastsirinotecanpro-inflammatory response

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